Report from the Fourth International Congress of the Cell Transplant Society
by Randy Dorian, Vice-President
(March 29, 1999)
We have just returned from the Fourth International Congress of the Cell Transplant Society in Montreux, Switzerland. The natural splendor of Montreux was breathtaking and the Swiss people were very hospitable. The food was superb.
Some of the work, particularly in attempting to find solutions to the problem of islet supply, was encouraging. Less encouraging are prospects for islet transplants into immunosuppressed diabetics. Although cures of "surgical diabetes" are well-established, it seems that autoimmune diabetes cannot be cured the same way. The key problem is that diabetics have autoimmunity against beta cells (such autoimmunity is thought to be the cause of IDDM). The autoimmunity continues even when all the beta cells have been killed, and quickly reoccurs following islet implantation. It was clear at Montreux that there are no fresh concepts to fight this problem. Thus we believe that the bio-artificial pancreas approach remains the most promising because a successful device would prevent autoimmune recurrence as well as rejection.
While it was evident that some progress is being made in immunoisolation technology, it was disheartening to see that many people are still encapsulating islets in devices which are guaranteed by their design to kill islets or to fall apart over time in the body. Some investigators invoked subtle immunological explanations for the death of their islets when it was quite apparent that the mere certainty of islet starvation was sufficient to explain the results. This is the sort of thing that wastes time and resources and perpetuates confusion in the field. We would encourage our colleagues to be attentive to the well-established requirements for success which we have laid out here on our website and to consider simple common sense explanations when interpreting experimental results.
One exciting development was a report from Yoko Mullen's group at UCLA. Using encapsulation methods developed by ISM's Randy Dorian and UC-Davis, the UCLA group reported euglycemia in two diabetic dogs implanted with approximately 300,000 encapsulated islets each. Previously the UC-Davis group had reported one dog cured. There are literature reports of several large animals being cured with encapsulated islets; to our knowledge, this is the first encapsulation method to be confirmed in an independent laboratory.
Unfortunately, no one in Yoko's group was able to describe the reagents or methods used in their study. Bill Drake, representing Islet Tech, the company which Yoko explained was responsible for alginate purification and islet microencapsulation, was also unable to shed any further light on the matter, explaining that he is "not technical". During the discussion of the presentation it was suggested that reagent standardization would be a good thing. As it happens, we know that the unidentified biocompatible alginate and unspecified encapsulation methods employed in the reported study were all based on Randy's inventions assigned to the University of California, license to which is held by Islet Tech.
It is frustrating to us that useful methods which have been available for some time are not benefiting the research community because they are not widely known. The purpose of patents is to provide protection of inventors' intellectual property interests while making ideas and discoveries available by public disclosure to stimulate further technological advance. Unfortunately, patents are rarely read by academicians because they are not subjected to peer review before publication and many patents lack scientific merit. When utility of a patent is demonstrated, it is appropriate to cite the patent when reporting one's findings so that others can build on the success.
In the interest of helping out those investigators who continue to have problems with foreign body reactions to their alginate preparations and to encourage standardization of this commonly used reagent, we are adding a new section to our website entitled "Useful Methods". In addition to simple step-by-step recipes for alginate purification, as time permits we will continually be adding to this section proven methods for microencapsulation, including those used in the above noted study, useful assays and a variety of handy tips and pointers for researchers in the field. We encourage anyone who has alternative methods or other useful tips to submit them to us for posting to this page. Final judgment for posting these methods will be made by ISM. We will not publish any bad methods. Please feel free to contact us if you need further technical details on posted methods or have any questions about these or other methods. Our hope is to provide a resource of valuable tools which will help our colleagues to progress more efficiently toward our common goal of curing juvenile diabetes.
Although the people with whom we spoke felt that the presentation by Mullen's group was confused, we are nevertheless pleased that she and her coworkers have successfully cured a couple pancreatectomized dogs using the University of California methods. The two dogs have been off insulin for a few weeks. We believe that if Islet Tech followed the UC/Dorian methods carefully, these dogs should remain euglycemic indefinitely. The results corroborate and help to legitimize the controversial results obtained with Kent Cochrum at UC Davis. Kent's dog has been euglycemic now for over four years. Yoko's and Kent's results would confirm many of the basic premises upon which Islet Sheet's technology is based. The Sheet achieves all the criteria satisfied by the UC microcapsules and additionally provides greater control over permeability, which may be important in the xenograft situation, as well as offering other advantages, including retrievability and compactness.
We hope that, with our help, other islet laboratories will confirm that thin encapsulation with "bioinvisible" alginate can be used to achieve euglycemia without immune suppression. We believe this will lead to a new era in islet implantation.